Abstract

Neurotropic viruses that conditionally infect or replicate
in molecularly defined neuronal subpopulations,
and then spread transsynaptically, are powerful tools
for mapping neural pathways. Genetically targetable
retrograde transsynaptic tracer viruses are available
to map the inputs to specific neuronal subpopulations,
but an analogous tool for mapping synaptic
outputs is not yet available. Here we describe a Cre
recombinase-dependent, anterograde transneuronal
tracer, based on the H129 strain of herpes simplex
virus (HSV). Application of this virus to transgenic
or knockinmice expressing Cre in peripheral neurons
of the olfactory epithelium or the retina reveals widespread,
polysynaptic labeling of higher-order
neurons in the olfactory and visual systems, respectively.
Polysynaptic pathways were also labeled from
cerebellar Purkinje cells. In each system, the pattern
of labeling was consistent with classical circuittracing
studies, restricted to neurons, and anterograde
specific. These data provide proof-of-principle
for a conditional, nondiluting anterograde transsynaptic
tracer for mapping synaptic outputs from
genetically marked neuronal subpopulations.